文章：

异常ERBB家族信号调控的抗肿瘤免疫

Antitumour immunity regulated by aberrant ERBB family signalling

原文发布日期：2021-01-18

DOI: 10.1038/s41568-020-00322-0

类型: Review Article

开放获取: 否

英文摘要：

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. Molecular-targeted agents against these signalling pathways exhibit robust clinical efficacy, but patients inevitably experience acquired resistance to these molecular-targeted therapies. Although cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have shown durable antitumour response in a subset of the treated patients in multiple cancer types, clinical efficacy is limited in cancers harbouring activating gene alterations of ERBB family members. In particular, ICI treatment of patients with non-small cell lung cancers with epidermal growth factor receptor (EGFR) alterations and breast cancers with HER2 alterations failed to show clinical benefits, suggesting that EGFR and HER2 signalling may have an essential role in inhibiting antitumour immune responses. Here, we discuss the mechanisms by which the signalling of ERBB family members affects not only autonomous cancer hallmarks, such as uncontrolled cell proliferation, but also antitumour immune responses in the tumour microenvironment and the potential application of immune-genome precision medicine into immunotherapy and molecular-targeted therapy focusing on the signalling of ERBB family members.

摘要翻译： 

ERBB家族成员的异常信号传导在多种恶性肿瘤的肿瘤发生及抗肿瘤免疫逃逸中扮演重要角色。针对这些信号通路的分子靶向药物虽展现出显著的临床疗效，但患者不可避免地会出现获得性耐药。尽管包括免疫检查点抑制剂（ICIs）在内的癌症免疫疗法在部分多种癌症患者中显示出持久的抗肿瘤反应，但在携带ERBB家族成员激活基因改变的癌症中，其临床疗效有限。特别是，对伴有表皮生长因子受体（EGFR）改变的非小细胞肺癌和伴有HER2改变的乳腺癌患者进行ICI治疗未能显现临床获益，这表明EGFR和HER2信号可能在抑制抗肿瘤免疫反应中起关键作用。本文探讨了ERBB家族成员信号传导不仅影响自主性癌症特征（如不受控的细胞增殖），还影响肿瘤微环境中抗肿瘤免疫反应的机制，以及免疫-基因组精准医学在针对ERBB家族信号通路的免疫治疗和分子靶向治疗中的潜在应用。

原文链接：

Antitumour immunity regulated by aberrant ERBB family signalling